We have found a new Borrelia spirochete that causes persistent infection in laboratory mice and is widely distributed in field populations of Ixodes tick vectors of Lyme disease throughout the United States. Preliminary genetic and antigen analysis indicates that this organism is a member of a closely related group of relapsing fever spirochetes and was originally described as Borrelia miyamotoi in Japan. Recent investigations provide convincing evidence that this spirochete causes human disease in Russia where the percentages of B. miyamotoi-infected Ixodes ticks are similar to those in the northeastern United States. Some of these patients experienced prolonged, relapsing illness. Basic information is lacking regarding genetic and antigenic characteristics of this novel spirochete and diagnostic tools are not yet developed for clinical use. Although only a few human cases of infection with B. miyamotoi are currently recognized, we suspect that cases may exist elsewhere within its broad geographic distribution and particularly in the northeastern United States where Lyme disease is hyperendemic. Accordingly, we propose to investigate the antigenic relationship between B. miyamotoi and other Borrelia species in order to develop improved diagnostic methods and to compare the frequency and clinical manifestations of B. miyamotoi infection with those of Borrelia burgdorferi in the Northeast. Such information is urgently needed because of the high level of human exposure to bites from ticks potentially infected with B. miyamotoi in Lyme endemic regions and because infection cannot be detected with the same laboratory procedures used to diagnose Lyme disease. Because B. miyamotoi belongs to the relapsing fever group of spirochetes and causes persistent illness with relapsing fever symptoms, it is possible that some prolonged episodes of illness attributed to Lyme disease and designated as chronic Lyme disease are due to B. miyamotoi infection.